Biology subjects

Lin, P.

Publications and source records attributed to Lin, P..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Evolution of chronic lymphocytic leukemia after allogeneic stem cell transplant

Allogeneic stem cell transplant (alloSCT) for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) can result in cure in some patients. Analogous to chemotherapy and targeted therapy, we hypothesized that allogeneic cellular immunotherapies, including alloSCT and donor lymphocyte infusion (DLI), would impact malignant evolution through the application of selective immunologic pressure with reciprocal changes in the T cell compartment. We tested a cohort of 24 patients treated with HLA-matched alloSCT +/- DLI, two mediators of the graft versus leukemia (GVL) effect. Comparison of pre-alloSCT samples revealed that a key difference between responders (n=13) and non-responders (n=11) is the cellularity of leukemic cells. We further mapped mutational trajectories of tumor cells by whole exome sequencing (WES) of sort-purified CLL in 11 post-transplant relapsed patients and found evidence of subclonal leukemic evolution in 8/11 patients after nonmyeloablative human leukocyte antigen (HLA)-matched alloSCT. Different patterns of CLL evolution were observed, and these changes included putative CLL drivers in every case. To investigate the presence of immune-related variants in patients, we collected 19 T cell co-culture CRISPR datasets and identified the top positive and negative regulators of cancer cells response to T-cell-dependent killing. We found that most mutations linked to T-cell killing emerged after allo-SCT treatment, suggesting that selective pressures from the GVL effect may drive the evolution of these mutations. Together, these data identify cellular homogeneity as a key biomarker for susceptibility to GVL-driven immunity in CLL and illustrate how the leukemic cells further evolve to evade immunosurveillance. SIGNIFICANCEThe impact of allogeneic stem cell transplant (alloSCT) on subclonal leukemia evolution remains poorly understood. By performing whole exome sequencing (WES) on pre- and post-alloSCT patient samples, we reveal different patterns of CLL evolution and potential immune-related driver genes influencing CLL relapse and refractory disease post-alloSCT.

cancer biology↗

bioRxiv2024

Deep Learning Unravels Potential Antibiotic-Resistance Drugs against Klebsiella Pneumoniae

BackgroundKlebsiella pneumoniae (KP) is a critical pathogen recognized by the World Health Organization due to its high mortality rates and resistance to antibiotics. Developing effective treatments for KP is essential to mitigate the growing threat of multidrug-resistant infections. This study leverages deep learning techniques to identify and validate potential drug candidates against KP, accelerating the drug discovery process and reducing associated risks. ResultsA comprehensive dataset was constructed, comprising 3,475 drugs selected from the DrugBank database, filtered for their potential efficacy and safety. Using convolutional neural networks (CNNs) for drug-drug interaction analysis, a prediction accuracy of 72% was achieved. Evolutionary Scale Modeling (ESM) was employed to calculate molecular similarities between drugs and KP strains, identifying five promising candidates with structural similarities exceeding 85% to known KP targets. A drug repurposing knowledge graph (DRKG) further validated these findings, with the PairRE model outperforming other approaches in ranking potential drug candidates. ConclusionsThis study presents a scalable and efficient framework for identifying and validating drug candidates to combat antibiotic-resistant KP. By integrating deep learning models, molecular similarity analysis, and knowledge graph techniques, this approach shortens the drug discovery timeline from years to months. The identified candidates hold significant promise for preclinical and clinical testing, offering a pathway to effective therapies against KP and other multidrug-resistant pathogens.

bioinformatics↗

bioRxiv2024

Deep Learning with Evolutionary Scale Modeling to discover Antibiotic-Resistance Drug against Klebsiella Pneumoniae

The development of effective antibiotics is crucial in combating antibiotic-resistant pathogens such as Klebsiella pneumoniae (KP). This study utilizes deep learning, specifically Evolutionary Scale Modeling (ESM), to identify potential drug candidates. By analyzing molecular similarities between known drugs and KP strains, we aim to accelerate the discovery of new treatments and reduce the risks associated with clinical trials. This approach may shed new lights in the field of drug repositioning.

bioinformatics↗

bioRxiv2024

Interpreting Sleep Activity Through Neural Contrastive Learning

Memories are spontaneously replayed during sleep, a process thought to support memory consolidation. However, capturing this replay in humans has been challenging because unlike wakefulness, sleep EEG is dominated by slow, rhythmic background activity. Moreover, each sleep stage (e.g., NREM, REM) has distinct rhythms, hindering generalisation of models trained on wake-state data. To overcome these challenges, we developed the Sleep Interpreter (SI), a neural network model that decodes memory replay from sleep EEG. In a large dataset comprising 135 participants ([~]1,000 h of overnight sleep; [~]400 h of wake), we employed a TMR-like paradigm with 15 semantically congruent cue-image pairs to tag specific memories. SI was trained separately for NREM and REM using contrastive learning to align neural patterns across wake and sleep, filtering out stage-specific background rhythms. We also examined how slow oscillations and spindle coupling influence decoding in NREM sleep. In a 15-way classification, SI achieved up to 40.02% Top-1 accuracy on unseen subjects. To test generalisability, we followed up with two independent nap experiments in separate samples and applied the trained SI model off-the-shelf. The first probed spontaneous reactivation without auditory cues, while the second used semantic-free sounds with new images. In both, SI successfully decoded reactivation during sleep that correlated with post-nap memory performance. By openly sharing our dataset and SI system, we provide a unique resource for advancing research on memory and learning during sleep, and related disorders.

neuroscience↗

bioRxiv2024

THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression

ABSTRACTGlioblastoma (GBM), the most common and aggressive malignant brain tumor in adults, has a median survival of 21 months. To identify drivers of GBM proliferation, we conducted a CRISPR-knockout screen, which revealed THO Complex 1 (THOC1) as a key driver. Knocking down THOC1 significantly reduced GBM cell viability across patient-derived xenograft (PDX) lines, enhancing survival (p<0.01) in primary PDX models. Conversely, overexpressing THOC1 in non-cancerous cells bolstered viability, decreasing survival and causing tumor engraftment in vivo (p<0.01). Further investigation revealed THOC1s robust interaction with SIN3A, a histone deacetylase complex. Histone deacetylation has been previously shown to prevent the buildup of R-loops, structures that form normally during transcription but can be lethal in excess. We found that THOC1-knockdown leads to elevated R-loop levels and reduced histone deacetylation levels. Next, to understand the networks specifically regulated by THOC1-mediated R-loop prevention, we conducted unbiased RNA-sequencing on control and THOC1-knockdown GBM cells. We found that THOC1s role in R-loop prevention primarily affects telomeres, critical regions for cell replication. We further show that THOC1-knockdown results in significantly increased telomeric R-loop levels and shortened telomeres. Ultimately, this study suggests that targeting THOC1 shows promise as a therapeutic strategy to disrupt the delicate R-loop landscape and undermine GBMs replicative potential.

cancer biology↗

bioRxiv2024

Macrophages facilitate interclonal cooperation-induced tumor heterogeneity and malignancy by activating the innate immune signaling

Tumor heterogeneity is a common hallmark of cancer and is considered a major cause of treatment failure and relapse, yet it remains poorly understood how various types of cells communicate within the tumor microenvironment (TME) to regulate tumor progression in vivo. Here we establish a tumor heterogeneity model in Drosophila eye epithelium by mutating the tricellular junction protein M6 in cells surrounding RasV12benign tumors and dissect the in vivo mechanisms underlying interclonal cooperation-induced malignancy by utilizing sophisticated genetic techniques in conjunction with single-cell RNA sequencing (scRNA-seq). Our findings reveal that loss of M6 facilitates the malignant transformation of neighboring RasV12 tumors by activating the Toll signaling, the innate immune response pathway. Notably, inhibiting Toll signaling impedes tumor progression, whereas its activation synergistically promotes RasV12 tumor malignancy by inactivating the Hippo pathway. Mechanistically, RasV12 tumors surrounded by M6 mutant clones lead to increased recruitment of hemocytes, which are the equivalent of macrophages in Drosophila, in a JNK pathway-dependent manner. Consequently, these tumor-associated macrophages secrete the Spatzle (Spz) ligand, which subsequently activates the Toll receptor within the RasV12 tumors, thereby triggering tumorigenesis. In summary, our study elucidates the complex in vivo interactions between genetically distinct oncogenic cells and between tumors and macrophages, shedding light on how macrophages exploit the innate immune signaling within tumors to regulate tumor heterogeneity and promote tumor progression. Significance statementIntratumoral heterogeneity profoundly affects cancer development and treatment in human tumors. The intricate nature of tumor cells and the presence of diverse cell types pose challenges to uncovering in vivo mechanisms responsible for heterogeneity. Our Drosophila tumor heterogeneity model reveals that fruit fly macrophages promotes both tumor heterogeneity and malignancy. Following recruitment by tumor cells, these macrophages secrete the ligand Spz to activate the Toll signaling pathway within tumor cells, which subsequently inactivates the Hippo pathway to drive tumorigenesis. Our study highlights the crucial role of hemocytes as intermediaries in coordinating tumor heterogeneity and facilitating intercellular communication between different cells within the TME.

cancer biology↗

bioRxiv2024

Nuclear receptor E75/NR1D2 drives tumor malignant transformation by integrating Hippo and Notch pathways

Hormone therapy resistance and the ensuing aggressive progression of tumors present a significant clinical challenge. However, the mechanisms underlying the induction of tumor malignancy by hormone inhibition remain poorly understood. Here we show that Drosophila malignant epithelial tumors exhibit a comparable decrease in ecdysone signaling, the primary steroid hormone pathway in Drosophila. Furthermore, we find that ectopic expression of the nuclear receptor E75 partially mimics ecdysone signaling inhibition, specifically promoting the malignant transformation of benign tumors by integrating the Hippo and Notch signaling pathways. Genome-wide DNA binding profiles and biochemistry data reveal that E75 not only physically interacts with the transcription factors of both Hippo and Notch pathways, but also exhibits widespread co-binding to their target genes, thus contributing to tumor malignancy. Moreover, we validate these findings by demonstrating that depletion of NR1D2, the mammalian equivalent of E75, inhibits the activation of Hippo and Notch target genes, impeding glioblastoma progression in vivo. In summary, our study unveils a previously unrecognized mechanism by which hormone inhibition promotes tumor malignant transformation, while providing a conserved mechanistic understanding of how Hippo and Notch pathways are integrated by the oncogene E75/NR1D2 during tumor progression.

cancer biology↗

bioRxiv2024

PTBP1 mediates Sertoli cell actin cytoskeleton organization by regulating alternative splicing of actin regulators

Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics is controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms.

molecular biology↗

bioRxiv2024

CFI-1/ARID3 functions unilaterally to restrict gap junction formation in C. elegans

Electrical coupling is vital to neural communication, facilitating synchronized activity among neurons. Despite its significance, the precise mechanisms governing the establishment of gap junction connections between specific neurons remain elusive. Here, we identified that the PVC interneuron in Caenorhabditis elegans forms gap junction connections with the PVR interneuron. The transcriptional regulator CFI-1/ARID3 is specifically expressed in the PVC but not PVR interneuron. Reducing cfi-1 expression in the PVC interneuron leads to enhanced gap junction formation in the PVR neuron, while ectopic expression of cfi-1 in the PVR neuron restores the proper level of gap junction connections in the PVC neuron, along with the normal touch response. These findings unveil the pivotal role of CFI-1/ARID3 in bidirectionally regulating the formation of gap junctions within a specific neuronal pair, shedding light on the intricate molecular mechanisms governing neuronal connectivity in vivo. SUMMARY STATEMENTProper electrical coupling could be achieved by either of the partner cells; however distinctive influence on neuron circuits maybe achieved.

developmental biology↗

bioRxiv2024

Multi-layered Network Analysis of Osteoking in the Treatment of Osteoporosis: Unraveling Mechanisms from Gene Expression to Molecular Docking

This study aimed to elucidate the therapeutic mechanisms of Osteoking in the treatment of osteoporosis through a comprehensive analysis of potential targets, active ingredients, and associated pathways. MethodThe study employed an integrated approach to understand the molecular mechanisms underlying Osteokings treatment of osteoporosis. The construction of the protein-protein interaction network involved analyzing data from GENEMANIA and STRING databases. KEGG enrichment analysis was performed to identify enriched pathways, focusing on the cAMP signaling and PI3K-AKT signaling pathways. Active ingredients, disease targets, and osteoporosis-related pathways were integrated into a comprehensive network diagram using Cytoscape. ResultThe Gene Expression Omnibus (GEO) database was employed to identify osteoporosis-related gene targets, revealing 3,578 downregulated and 1,204 upregulated genes. Simultaneously, Osteokings active ingredients and potential targets were investigated using the Traditional Chinese Medicine Integrated Database (ETCM). A protein-protein interaction network and KEGG pathway enrichment analysis were constructed, highlighting potential targets for Osteokings therapeutic effects on osteoporosis. The study also conducted molecular docking analysis, revealing the strong binding capacities of Kaempferol with key disease targets. The results suggest that Osteoking, particularly its active component Kaempferol, holds promise as a potential intervention for osteoporosis, providing insights for further exploration and development of osteoporosis treatments ConclusionsIn conclusion, despite some limitations, this study provides valuable information for the treatment of osteoporosis. Future research should make further progress by continually expanding data sources, conducting in-depth experimental validations, and broadening the scope of targets to better understand and address this common skeletal disorder. FundingThis work was supported by the Scientific Foundation of Fuzhou Municipal Health Commission (2021-S-wp3).

bioinformatics↗

bioRxiv2024

Exploring Mechanisms of Lipid Nanoparticle-Mucus Interactions in Healthy and Cystic Fibrosis Conditions

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerged as versatile non-viral gene delivery systems that could help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics simulations. Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/575680v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@10b1c0dorg.highwire.dtl.DTLVardef@5ebce4org.highwire.dtl.DTLVardef@1c34c1corg.highwire.dtl.DTLVardef@b9eb2d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

SOAPy: a Python package to dissect spatial architecture, dynamics and communication

Advances in spatial omics technologies have brought opportunities to dissect tissue microenvironment, while also posing more requirements and challenges for computational methods. Here we developed a package SOAPy to systematically dissect spatial architecture, dynamics and communication from spatial omics data. Specifically, it provides analysis methods for multiple spatial-related tasks, including spatial domain, spatial expression tendency, spatiotemporal expression pattern, cellular co-localization, multi-cellular niches, and ligand-receptor-mediated and spatial-constrained cell communication. Applying SOAPy on different spatial omics technologies and diverse biological fields has demonstrated its power on elucidation of biological questions about tumors, embryonic development, and normal physiological structures. Overall, SOAPy is a universal tool for spatial omics analysis, providing a foundation for continued investigation of the microenvironment.

bioinformatics↗

bioRxiv2023

GeneMAP: A discovery platform for metabolic gene function

Organisms maintain metabolic homeostasis through the combined functions of small molecule transporters and enzymes. While many of the metabolic components have been well-established, a substantial number remains without identified physiological substrates. To bridge this gap, we have leveraged large-scale plasma metabolome genome-wide association studies (GWAS) to develop a multiomic Gene-Metabolite Associations Prediction (GeneMAP) discovery platform. GeneMAP can generate accurate predictions, even pinpointing genes that are distant from the variants implicated by GWAS. In particular, our work identified SLC25A48 as a genetic determinant of plasma choline levels. Mechanistically, SLC25A48 loss strongly impairs mitochondrial choline import and synthesis of its downstream metabolite, betaine. Rare variant testing and polygenic risk score analyses have elucidated choline-relevant phenomic consequences of SLC25A48 dysfunction. Altogether, our study proposes SLC25A48 as a mitochondrial choline transporter and provides a discovery platform for metabolic gene function.

genomics↗

bioRxiv2023

hURAT1 Transgenic Mouse Model for Evaluating Targeted Urate-Lowering Agents

ObjectiveUrate transporter 1 (URAT1), a well-established urate-lowering therapeutic target for hyperuricemia and gout treatment, expresses in the kidney proximal tubule and is responsible for uric acid (UA) reabsorption. However, non-primate animal models currently used in pharmacological studies failed to evaluate URAT1 inhibitors effectiveness because their URAT1 has a very low UA affinity compared to human URAT1, resulting in a lag in targeting drug screening and novel therapy development for gout treatment. We established a human URAT1 (hURAT1) transgenic knock-in (KI) mouse model to assess uricosuric agents effectiveness and characterize URAT1-caused pathogenesis. MethodsWe generated hURAT1 transgenic mice using CRISPR/Cas9 knock-in technique. mUrat1 knockout was achieved by replacing exon 1 coding sequence with a human SLC22A12 CDS-pA cassette. Based on the above transgenic mice, a hyperuricemia model was further established by hypoxanthine administration. ResultsThe hURAT1-KI mice successfully expressed hURAT1 protein to the apical side of the kidney proximal tubule epithelium, where a native human URAT1 kidney localization in human body. Upon hypoxanthine challenge, the blood UA level was elevated in hURAT1-KI mice, exhibiting an approximately 37% increase compared to wild-type (WT) mice. The elevated blood UA level could be alleviated by hURAT1 inhibitor benzbromarone treatment in the hURAT1-KI mice whereas no response was observed in WT littermates. Therefore, hURAT1 transgenic mice responded well to inhibitors and can be used to evaluate the therapeutic effects. ConclusionThe hURAT1-KI hyperuricaemia mouse model would be valuable for preclinical evaluation of urate-lowering agents toward gout treatment and studying UA metabolic complexities in humans.

pharmacology and toxicology↗

bioRxiv2023

Injury induced renal fibrosis promotes cystogenesis and cyst growth in adult mice with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a life-long disease and caused by mutations in PKD1 or PKD2 gene. Fibrosis is a hallmark of chronic kidney disease and is positively correlated with renal cyst growth, however the role of fibrosis in ADPKD is still controversial. In this study, we established renal fibrosis by toxic or surgical injuries in adult mice, and Pkd gene was inactivated at different time point before or after renal injury according to the pattern of fibrosis progression in different injury models. Here we showed that renal injury before or after Pkd gene inactivation can both induce renal cysts in adult Pkd1 or Pkd2 mice, and the extent of cystic burden was tightly correlated with the baseline levels of fibrosis when three hits (injury and gene inactivation) occurred. Inactivation of Pkd1 gene at the recovery stage after surgery induced less renal cysts in adult Pkd1 mice. Enhanced renal fibrosis by repeated toxic injuries before gene inactivation accelerated renal cyst growth in Pkd1 mice. We further showed that the rate of cyst formation at the early stage in adult Pkd1 mice was positively correlated with the baseline levels of renal fibrosis. Finally, we showed that conditional knockout of Ezh2 gene attenuated renal fibrosis and cyst growth in adult Pkd1 mice with pre-existing renal fibrosis. We conclude that the fibrotic response after renal injury is a driving force for renal cyst formation and growth in adult kidneys and inhibition of renal fibrosis through targeting EZH2 might be new therapeutic strategy for adult ADPKD. Importantly, our study suggests that there is a time window for intervention upon acute kidney injury in adult ADPKD patients. Translational StatementAutosomal dominant polycystic kidney disease (ADPKD) is a life-long disease and caused by mutations in PKD1 or PKD2 gene. Fibrosis is a hallmark of chronic kidney disease and is positively correlated with renal cyst growth, however the role of renal fibrosis in ADPKD is controversial. In this study, we found that renal cysts were formed in adult Pkd1 or Pkd2 mice with established renal fibrosis induced by toxic or ischemia reperfusion injuries. Cyst formation or growth in adult ADPKD mice was tightly correlated with baseline levels of renal fibrosis after third hits. Enhanced renal fibrosis before Pkd1 gene deletion in adult mice accelerated cyst growth. Inhibition of renal fibrosis through targeting EZH2 delayed cyst growth in adult ADPKD mice. Thus, renal fibrosis is a trigger of cyst formation and growth in adult ADPKD mice, and therapeutically targeting EZH2 might be new strategy to treat adult patients with ADPKD. Our study suggests that there is a time window for intervention upon acute kidney injury in adult ADPKD patients.

pathology↗

bioRxiv2023

Discovery of fibrotic intervertebral disc in mice

Intervertebral discs are crucial to spine flexibility and stability during locomotion, but the mechanism of their mechanoadaptation to stress remains inadequately elucidated. We discovered spontaneous collagenesis in discs at the tail base in mice occurring from 14 days post-natal development. These discs termed as type C, differ from typical discs by exhibiting intensive collagen II and reduced aggrecan deposition contributing to the stiffening of the extracellular matrix (ECM), without typical degenerative markers. The reinforced mechanical properties enable type C discs to withstand high mechanical stress during flexion. Further analysis revealed that type C discs experience a turnover in cell composition, with the emergence of Procr+ progenitor cells and depletion of notochord cells. We demonstrated the essential role of mechanical stress in type C disc formation, suggesting a mechanoadaptive process rather than a pathological condition. Mechanistically, we identified TRPV4, as pivotal factors in collagen II synthesis in type C discs, highlighting the role of mechanotransduction in this adaptation. Our findings introduce a novel mechanoadaptive process of intervertebral disc by orchestrating collagenesis, advancing understanding of diverse disc functions in spine development and homeostasis, thereby providing insights for leveraging this mechanism to address spinal disorders.

pathology↗

bioRxiv2023

Transcription factor ScWRKY4 in sugarcane negatively regulates the resistance to pathogen infection through the JA signaling pathway

WRKY transcription factor, the transcriptional regulators unique to plants, plays an important role in plant defense response to pathogen infection. However, the disease resistance mechanism of WRKY gene in sugarcane remains unclear. Previously, we identified a ScWRKY4 gene, a member of class IIc of the WRKY gene family, from the sugarcane cultivar ROC22. This gene could be induced by the stresses of salicylic acid (SA) and methyl jasmonate (MeJA). Interestingly, the expression of the ScWRKY4 gene was down-regulated in smut-resistant sugarcane cultivars but up-regulated in smut-susceptible sugarcane cultivars under Sporisorium scitamineum stress. Besides, stable overexpression of the ScWRKY4 gene in Nicotiana benthamiana enhanced susceptibility to Fusarium solani var. coeruleum and caused the down-regulated expression of immune marker-related genes. Furthermore, transcriptome analysis indicated that, the expression of most JAZ genes was suppressed in plant signal transduction pathway. In addition, ScWRKY4 could interact with ScJAZ13 and repress the expression of ScJAZ13. We thus hypothesized that the ScWRKY4 gene was involved in the regulatory network of plant disease resistance, most probably through the JA signaling pathway. The present study depicted the molecular mechanism of the ScWRKY4 gene involved in sugarcane disease resistance and laid the foundation for the subsequent investigation. HighlightTransgenic plants overexpressing the ScWRKY4 gene negatively regulated resistance to pathogen by inhibiting the expression of the JAZ genes.

plant biology↗

bioRxiv2023

High-Resolution Characterization of Human Brain Cortex with High-Fidelity Spatial Transcriptomic Slides (HiFi-Slides)

Spatial transcriptomic tools and platforms help researchers to inspect tissues and cells with fine details of how they differentiate in expressions and how they orient themselves. With the higher resolution we get and higher throughput of expression targets, spatial analysis can truly become the core player for cell clustering, migration study, and, eventually, the novel model for pathological study. We present the demonstration of HiFi-slide, a whole transcriptomic sequencing technique that recycles used sequenced-by-synthesis flow cell surfaces to a high-resolution spatial mapping tool that can be directly applied to tissue cell gradient analysis, gene expression analysis, cell proximity analysis, and other cellular-level spatial studies.

bioengineering↗